Camrelizumab Combo Garners Significant PFS, OS Benefit in Unresectable HCC

A new drug application for rivoceranib and camrelizumab for unresectable HCC was accepted by the FDA in July 2023.

Patients with unresectable hepatocellular carcinoma (HCC) experienced a statistically significant and clinically meaningful improvement in survival outcomes following treatment with camrelizumab and rivoceranib vs sorafenib (Nexavar), according to results from the phase 3 CARES-310 study (NCT03764293).¹

With a median follow-up of 14.5 months (IQR, 9.1-18.7), those who received camrelizumab and rivoceranib experienced a median overall (OS) survival of 22.1 months (95% CI, 19.1-27.2) compared with 15.2 months (95% CI, 13.0-18.5) among those who were treated with sorafenib (HR, 0.62; 95% CI, 0.49-0.80; P <.0001). Additionally, the 12-month OS rate was 76.5% (95% CI, 71.0%-81.1%) vs 60.8% (95% CI, 54.6%-66.4%) and 60.9% (95% CI, 54.2%-66.9%) vs 45.2% (95% CI, 38.8%-51.4%) at 18 months in the camrelizumab arm and sorafenib arm, respectively.

Moreover, the median progression-free survival (PFS) was 5.6 months (95% CI, 5.5-6.3) in the camrelizumab arm compared with 3.7 months (95% CI, 2.8-3.7) in the sorafenib arm (HR, 0.52; 95% CI, 0.41-0.65; P <.0001). The median follow-up was 7.8 months (IQR, 4.1-10.6) Additionally, the 6-month PFS rate was 48.2% (95% CI, 41.9%-54.3%) in the camrelizumab cohort vs 25.3% (95% CI, 19.8%-31.1%) in the sorafenib cohort; the corresponding rates at 12 months were 29.8% (95% CI, 24.1%-35.8%) vs 12.4% (95% CI, 8.3%-17.3%), respectively.

“As evidenced in the CARES-310 study, camrelizumab plus rivoceranib demonstrate significant promise as a potentially improved therapy for advanced hepatocellular carcinoma,” Saeho Chong, chief executive officer at Elevar said in a press release on the study’s findings.² “Elevar is pleased The Lancet…recognized the significance of these results as we continue to work toward commercial development of this combined therapy.”

The open-label, global trial took place at 95 centers in 13 countries. Those who enrolled on the trial needed to be 18 years or older with disease that had been confirmed via histopathology or cytology. Patients also needed to have Barcelona Clinic Liver Cancer stage B or C disease for which surgery or locoregional therapy was not an option or experienced progression following the aforementioned treatments. At least 1 lesion evaluable via RECIST 1.1 criteria, Child-Pugh class A liver function, ECOG performance status of 0 or 1, life expectancy of 12 weeks or more, and adequate organ function were also required.

Those who enrolled on the trial (n = 842) and were eligible (n = 543) were randomly assigned 1:1 to be treated with either 200 mg of intravenous camrelizumab every 2 weeks and 250 mg of oral rivoceranib (n = 272), or 400 mg of oral sorafenib twice a day (n = 271).

The study’s dual primary end points were PFS by blinded independent central review and OS, with key secondary end points including PFS via investigator assessment, overall response rate, disease control rate, duration of response, and time to progression.

At baseline, investigators reported an alpha-fetoprotein concentration of at least 400 ng/mL in 36% of patients. Moreover, 75% of patients had hepatitis B virus etiology, and 74% had macrovascular invasion, extrahepatic metastasis, or both.

According to additional trial findings, discontinuation of at least 1 study drug was necessary for 26% of patients in the experimental arm compared with 37% of those in the comparator arm. Thirty-three percent and 48% of patients in each respective arm required a subsequent systemic treatment including targeted agents (30% vs 40%) and immunotherapy agents (15% vs 33%).

A total of 41% of patients in the experimental arm and 56% of patients in the sorafenib arm died as of the data cutoff.

Treatment-related adverse effects (TRAEs) were reported in 97% of those treated with camrelizumab compared with 93% in the sorafenib arm. High-grade TRAEs were observed in 81% vs 52% of patients, respectively. Frequent grade 3/4 TRAEs included hypertension, palmar-plantar erythrodysesthesia syndrome, and aspartate aminotransferase and alanine aminotransferase increase.

A new drug application for rivoceranib and camrelizumab for unresectable HCC was accepted by the FDA in July 2023.³ The application was based on data from the phase 3 CARES-310 trial that were presented at the 2022 European Society for Medical Oncology Congress (ESMO).

References

1. Qin S, Chan Sl, Gu S, et al. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet Published online July 24, 2023. doi:10.1016/S0140-6736(23)00961-3
2. Elevar therapeutics announces publication of phase 3 CARES 310 study results in the LANCET. News release. Elevar Therapeutics. July 24, 2023. Accessed July 25, 2023. https://bit.ly/44L2TtJ
3. Elevar Therapeutics announces FDA acceptance for filing of new drug application for rivoceranib in combination with camrelizumab as a first-line treatment for unresectable hepatocellular carcinoma. News release. Elevar Therapeutics, Inc. July 17, 2023. Accessed July 25, 2023. https://shorturl.at/oxBC8